The specific aims of this proposal are: (a) To develop a highly convergent and stereo-controlled strategy for the synthesis of the anticancer natural product Superstolide A; (b) To develop new synthetic methodologies for the synthesis of the core structure of Superstolide A, including: (i) The use of a butenolide as a partner in a Double-Michael reaction; (ii) A study of halo-enol lactone as a latent acetylene functionality; (c) The molecular design, chemical synthesis, and biological testing of simpler biological mimics of Superstolide A and to identify the minimum pharmacophore responsible for anticancer activity The designed synthetic strategy is characterized by the following important features: (1) convergency; (2) brevity; (3) flexibility; and (4) enantioselectivity. A Double-Michael reaction followed by an anionic Oxy- Cope rearrangement will be employed in the synthesis of the bicyclic core structure. Julia olefination, Suzuki coupling, and intramolecular Horner- Emmons olefination will be three key reactions to assemble the target.